Interest in genetic testing among first-degree relatives of breast cancer patients

The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first-degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta =.15; P,.0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations. Prior to widespread availability of such testing, it will be critical to develop informed consent protocols to educate individuals about the benefits and limitations of predictive testing for this multifactorial disease. © 1995 Wiley-Liss, Inc.     

Mechanisms by which hapten conjugates of pneumococcal polysaccharide interfere with the challenge of anti-hapten memory cells.

Incubation of trinitrophenylated hemocyanin (TNP-KLH)-primed spleen cells with microgram amounts of 2,4-dinitrophenyl (DNP) or 2,4,6-trinitrophenyl (TNP) conjugates of pneumococcal polysaccharide type 3 (SIII) for as little as 5 min at 4 degrees C results in a specific "block" of the 19 S and 7 S adoptive memory response to TNP-KLH. This hapten-SIII-induced block of anti-hapten memory B cell responsiveness seems to be an example of specific receptor blockade.The block is specific and can be prevented by simultaneous incubation of the primed cells with hapten-protein conjugates which presumably compete with the hapten-polysaccharide for attachment to the B cell surface via anti-hapten Ig receptors. Removal via capping of these Ig receptors by exposure of TNP-KLH-primed memory cells to rabbit anti-mouse Fab serum for 45 min at 37 degrees C renders these cells refractory to the blocking effect of hapten-SIII. Once the hapten-SIII has attached to the memory cells, these blocked cells can be "rescued" (i.e. returned to a state of responsiveness) by incubating these cells with either mouse anti-SIII at 37 degrees C or rabbit anti-DNP serum at 4 degrees C. Since a papain digest of the IgG fraction of rabbit anti-DNP did not rescue the cells while the intact IgG did, a capping off of the TNP-SIII was proposed as the mechanims for this return to responsiveness of the hitherto blocked cells. A rescue was not seen by treatment of recipient mice with such B cell mitogens as dextran sulfate, endotoxin or purified protein derivative of tuberculin.     

Soluble egg antigen-stimulated T helper lymphocyte apoptosis and evidence for cell death mediated by FasL(+) T and B cells during murine Schistosoma mansoni infection

Granuloma formation around schistosomal eggs is induced by soluble egg antigens (SEA) and mediated by the activity of CD4(+) Th lymphocytes and their cytokines. Regulation of the inflammatory Th cell response during infection is still insufficiently understood. The hypothesis of this study was that activation-induced cell death (AICD) of CD4(+) T cells is involved in the immune inflammatory response. This study investigated the dynamics of splenic and granuloma CD4(+) Th cell apoptosis and Fas ligand (FasL) expression during the acute and chronic stages of murine schistosomal infection. Enhanced apoptosis of freshly isolated CD4(+) Th lymphocytes commenced after egg deposition and persisted during the peak and modulated phases of granuloma formation. After oviposition, CD4(+), CD8(+), and CD19(+) splenocytes and granuloma cells expressed elevated levels of FasL but FasL expression declined during the downmodulated stage of infection. In culture, SEA induced splenic and granuloma CD4(+) T-cell apoptosis and stimulated expression of FasL on splenic but not granuloma CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells. SEA-stimulated splenocytes and granuloma cells preferentially lysed a Fas-transfected target cell line. Depletion of B cells from SEA-stimulated splenic cultures decreased CD4(+) T cell apoptosis. Coculture of purified splenic B cells with CD4(+) T cells and adoptive transfer of purified B cells indicated that antigen-stimulated B cells can kill CD4(+) Th cells. However, CD4(+) T cells were the dominant mediators of apoptosis in the granuloma. This study indicates that AICD is involved in the apoptosis of CD4(+) T cells during schistosomal infection.     

胺碘酮合用小剂量β受体阻滞剂治疗老年阵发房颤临床观察

目的 比较胺碘酮与小剂量β受体阻滞剂合用对老年阵发性房颤的疗效。方法 回顾分析30名老年阵发房颤患者,根据房颤复律后维持用药的不同,分为3组：单用胺碘酮组（n=11);单用β阻滞剂组（n=9);胺碘酮与小剂量β阻滞剂合用组（n=10)。比较3组患者用药后12个月中房颤控制情况及心室率、心脏传导情况。结果 单用胺碘酮组显效率54．5％,有效率45．5％,无效率0％;单用β受体阻滞剂组显效率22．2％,有效率44．5％,无效率33．3％;胺碘酮与小剂量β受体阻滞剂合用治疗房颤,显效率90％,有效率10％,其疗效明显优于单用胺碘酮（P＜0．05）或单用β阻滞剂（P＜0．01）组,且未见明显副作用：3组间心室率未见显著差别。结论 胺碘酮与小剂β受体阻滞剂合用可有效地控制老年阵发性心房纤颤的发作。     

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

喉癌中EGFR基因扩增、表达及临床意义

目的研究喉癌中表皮生长因子受体(EGFR)基因的扩增、表达,探讨其在喉癌发生、发展中的作用及临床意义。方法采用差异PCR(differential PCR)方法检测40例喉鳞状细胞癌及配对癌旁正常组织中EGFR基因的扩增(即基因拷贝数增加);应用RT-PCR方法检测EGFR mRNA水平;应用SPSS13.0软件对数据进行统计学分析。结果喉癌组织中有13例(占32.5%)EGFR基因拷贝数增加,癌旁对照组中则未检测到(χ2=15.537,P<0.005);喉癌组织中EGFR mRNA平均积分光密度为872.356±62.340,癌旁对照组为346.425±57.380(t=5.959,P<0.001);喉癌组织分化程度越低,病理分期越晚,EGFR基因扩增和mRNA表达水平越高(P<0.05)。结论喉癌中EGFR基因在DNA水平上的扩增是EGFR mRNA过表达的原因之一,EGFR的扩增和过表达在喉癌的发生、进展中发挥一定作用。     

髂内动脉注入鸦油乳对狗正常膀胱组织影响的研究

目的 为鸦油乳掏膀胱肿瘤生长提供组织学依据。方法 正常狗随机分为：注药组（７只）和对照组（３只）,分别经髂内动脉注入鸦油乳０．１ｍｇ／ｋｇ、美蓝０．１ｍｌ／ｋｇ。１周后,随机活检膀胱各个部位作光镜及电镜观察。结果 注药组光镜可见粘膜上皮细胞脱落、坏死、肌层和浆膜充血、水肿、坏死以及急、慢性炎性细胞浸润;电镜发现在微血管内有鸦油乳微栓形成,并见细胞质膜结构的破坏。而对照组未发现明显变化。结论 鸦油乳     

鼠源性单克隆抗体F(ab′)2片段制备工艺

目的制备符合临床应用质量标准的鼠源性mAb F(ab′)2片段.方法采用胃蛋白酶消化小鼠腹水抗体,疏水作用色谱法纯化F(ab′)2片段的新工艺,替代原有的木瓜蛋白酶消化IgG,阴离子交换色谱法纯化的旧工艺.结果新工艺所制备的F(ab′)2 片段经SDS-PAGE检测纯度达98%以上,ABC免疫组化法测定免疫活性为1∶8000,回收率大于 50%,核酸含量及热原均合格,整个工艺流程可在48 h内完成.结论新工艺制备人用鼠源性mAb F(ab′)2片段更简便高效、安全实用,能够适应中试放大及大规模生产的要求.